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Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
eniluracil
conventional colon surgery
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage I colon cancer, stage II colon cancer, stage III colon cancer, stage IV colon cancer, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer

Eligibility Criteria

19 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion: DISEASE CHARACTERISTICS: Histologically proven or suspicious primary or metastatic colorectal carcinoma undergoing disease resection PATIENT CHARACTERISTICS:A. Age: 19 and over Performance status: Karnofsky 60-100% Not pregnant or nursing Fertile patients must use effective contraception during and for at least 1 month after study PRIOR CONCURRENT THERAPY: Subject has had at least 8 weeks since prior fluorouracil, capecitabine, fluorouracil-uracil, floxuridine, or S-1 Endocrine therapy: No prior or concurrent steroids Radiotherapy: Surgery: No prior emergent surgery (e.g., perforation or obstruction) No prior transplantation At least 8 weeks since any prior drug metabolized by dihydropyrimidine dehydrogenase enzyme At least 8 weeks since prior flucytosine Exclusion: Severe infection(White Blood Cell Count)WBC>2 times normal Fever Sepsis Subject on immunosuppressives therapy Subjects will serum Bilirubin/Creatinine>2 times normal levels Pregnant /Lactating women Subjects that have received eniluracil or 5-FU(Fluorouracil) within 28 days prior to randomization Subject that have comorbidity illnesses that will increase the likelihood of there death in <5 years

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Oral eniluracil 20 mg twice daily

    Placebo

    Arm Description

    20 mg of eniluracil given twice daily for duration of the study. This subject may have surgery IF tumor is amenable to resection

    20 mg placebo that will be given for the duration of the study. This subject may have surgery IF tumor is amenable to resection

    Outcomes

    Primary Outcome Measures

    Primary Goal to demonstrate that eniluracil at current clinical doses
    To see if at standard clinical doses are capable of inhibiting DPD in Primary and metastatic colorectal cancer in vivo. Since one of the mechanisms of 5-FU(Fluorouracil) tumor resistance is overexpression of DPD,effective inactivation DPD in tumors by eniluracil in this study will be supportive of the use of eniluracil to overcome this type of 5-FU(Fluorouracil) resistance

    Secondary Outcome Measures

    Evaluate DPD recovery and uracil levels
    To evaluate the recovery of DPD and uracil levels at 4 more times in the range of postoperative days 5-7,12-16,20-24,and 26-30.

    Full Information

    First Posted
    January 21, 2000
    Last Updated
    June 12, 2015
    Sponsor
    University of Alabama at Birmingham
    Collaborators
    National Cancer Institute (NCI), Glaxo Wellcome
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00004195
    Brief Title
    Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer
    Official Title
    Evaluation of Dihydropyrimidine Dehydrogenase (DPD) Activity in Surgically Resected Primary and Metastatic Colorectal Cancer After 48 hr Pretreatment With Eniluracil
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    September 1998 (undefined)
    Primary Completion Date
    October 1999 (Actual)
    Study Completion Date
    May 2001 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Alabama at Birmingham
    Collaborators
    National Cancer Institute (NCI), Glaxo Wellcome

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    RATIONALE: Eniluracil may increase the effectiveness of chemotherapy by blocking tumor enzymes that break down chemotherapy drugs. PURPOSE: Randomized phase II trial to determine the effectiveness of eniluracil followed by surgery in treating patients who have primary or metastatic colorectal cancer.
    Detailed Description
    OBJECTIVES: I. Determine the enzymatic activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells (PBMC), normal mucosa, or normal liver in patients with primary or metastatic colorectal cancer. II. Evaluate the ability of eniluracil to inactivate DPD in the tumor, PBMCs, and normal tissue in this patient population. III. Assess DPD recovery and uracil levels in PBMCs following surgical resection in these patients. OUTLINE: This is a randomized, placebo controlled study. Patients are stratified according to colorectal tumor (primary vs metastatic). Patients are randomized into one of two treatment arms. Arm I: Patients receive oral eniluracil twice daily on days -2 and -1 followed by surgical resection and tissue harvest on day 0. Arm II: Patients receive an oral placebo as in arm I followed by surgical resection and tissue harvest on day 0. Patients are followed weekly for 1 month. PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colorectal Cancer
    Keywords
    stage I colon cancer, stage II colon cancer, stage III colon cancer, stage IV colon cancer, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    28 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Oral eniluracil 20 mg twice daily
    Arm Type
    Active Comparator
    Arm Description
    20 mg of eniluracil given twice daily for duration of the study. This subject may have surgery IF tumor is amenable to resection
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    20 mg placebo that will be given for the duration of the study. This subject may have surgery IF tumor is amenable to resection
    Intervention Type
    Drug
    Intervention Name(s)
    eniluracil
    Other Intervention Name(s)
    5 Fu/eniluracil (eli Lilly), 5-fu/eniluracil, 5fu/eniluraci
    Intervention Description
    Will be given to either subject pre-operative and metastatic disease
    Intervention Type
    Procedure
    Intervention Name(s)
    conventional colon surgery
    Intervention Description
    Only if the subject is amenable to surgical resections
    Primary Outcome Measure Information:
    Title
    Primary Goal to demonstrate that eniluracil at current clinical doses
    Description
    To see if at standard clinical doses are capable of inhibiting DPD in Primary and metastatic colorectal cancer in vivo. Since one of the mechanisms of 5-FU(Fluorouracil) tumor resistance is overexpression of DPD,effective inactivation DPD in tumors by eniluracil in this study will be supportive of the use of eniluracil to overcome this type of 5-FU(Fluorouracil) resistance
    Time Frame
    Pre-operative and up to 30 days after first dose
    Secondary Outcome Measure Information:
    Title
    Evaluate DPD recovery and uracil levels
    Description
    To evaluate the recovery of DPD and uracil levels at 4 more times in the range of postoperative days 5-7,12-16,20-24,and 26-30.
    Time Frame
    pre-operative and up to 30 post first dose
    Other Pre-specified Outcome Measures:
    Title
    Specific Aims
    Description
    Determine the enzymatic activity of DPD in PBMC's normal mucosa or normal liver and in primary and secondary colorectal cancers Confirm the ability of eniluracil to inactivate DPD in tumors as well as PBMC's and normal tissue Assess DPD recovery and uracil levels in PBMC's at 5-7,12-16,20-24,and 26-30 days postoperatively
    Time Frame
    Duriation of trial up to 30 days after first dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    19 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion: DISEASE CHARACTERISTICS: Histologically proven or suspicious primary or metastatic colorectal carcinoma undergoing disease resection PATIENT CHARACTERISTICS:A. Age: 19 and over Performance status: Karnofsky 60-100% Not pregnant or nursing Fertile patients must use effective contraception during and for at least 1 month after study PRIOR CONCURRENT THERAPY: Subject has had at least 8 weeks since prior fluorouracil, capecitabine, fluorouracil-uracil, floxuridine, or S-1 Endocrine therapy: No prior or concurrent steroids Radiotherapy: Surgery: No prior emergent surgery (e.g., perforation or obstruction) No prior transplantation At least 8 weeks since any prior drug metabolized by dihydropyrimidine dehydrogenase enzyme At least 8 weeks since prior flucytosine Exclusion: Severe infection(White Blood Cell Count)WBC>2 times normal Fever Sepsis Subject on immunosuppressives therapy Subjects will serum Bilirubin/Creatinine>2 times normal levels Pregnant /Lactating women Subjects that have received eniluracil or 5-FU(Fluorouracil) within 28 days prior to randomization Subject that have comorbidity illnesses that will increase the likelihood of there death in <5 years
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Martin J. Heslin, MD
    Organizational Affiliation
    University of Alabama at Birmingham
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer

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